A drug screening system for ALS by automated, quantitative motility analysis of C. elegans ALS model

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670439
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: Sobue Gen 名古屋大学, 医学(系)研究科(研究院), 特任教授 (20148315)
• Co-Investigator(Kenkyū-buntansha): Katsuno Masahisa 名古屋大学, 大学院医学系研究科, 教授 (50402566)
• Co-Investigator(Renkei-kenkyūsha): Mori Ikue 名古屋大学, 大学院理学系研究科, 教授 (90219999)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 筋萎縮性側索硬化症 / 薬剤スクリーニング / 低分子化合物 / トランスレーショナルリサーチ / 線虫

Outline of Final Research Achievements

There has not been reliable method for in vivo high-throughput quantification of the drug effects. Recently our collaborator developed a real-time computer vision system, the Multi worm tracker(WMT), that can quantify the behavior of dozens of worms. Using this system, we explored the effective drug for the ALS model animals, dnc-1KD worm, in which the dynactin 1 is knocked down in the motor neurons. This model shows the motor neuronal degeneration, and it mimics a several significant features of ALS pathology. We first chose rapamycin as a positive control and showed the effect in a dose dependent manner. Next, we screened the 50 drugs and identified two compounds which significantly rescued the motor deficit of the worm. Interestingly, one of the drug was Riluzole, which is one of the only two drugs approved for ALS in Japan. The other drug X is an anti-hypertensive drug. This method allow us to complete a drug screen in a few weeks compared with a few years when using rodent models.

Free Research Field

神経内科学